Effects of Multi-strain Bacillus Spore Probiotics on Growth, Digestive Function, and Gut Microbiota in Cesarean-Delivered Neonates

NCT07320287 | Not Yet Recruiting DMC

• 1 other identifier: TNLS.2025.NB
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Infants born by cesarean section commonly show early weight loss and slower recovery of birth weight, together with characteristic patterns of gut microbiota dysbiosis marked by reduced Bifidobacterium and Bacteroides and increased Proteobacteria. This early microbial alteration has been associated with functional gastrointestinal disorders (FGIDs), including colic, regurgitation, and changes in stool frequency and consistency, which may in turn affect early growth and overall gastrointestinal functioning. Probiotic supplementation is considered a safe and feasible strategy to support microbial restoration and improve digestive function during the first months of life. In this study, researchers propose that daily supplementation with multi-strain Bacillus spore probiotics may help support healthy early growth, reduce functional gastrointestinal symptoms, and promote a more balanced gut microbiota in cesarean-delivered infants. The objective of this study is to evaluate the safety and efficacy of two oral probiotic formulations, LiveSpo PREG-MOM and LiveSpo CONSY, containing multi-strain B. subtilis ANA46, B. clausii ANA39, and B. coagulans ANA40 at respective 3 and 4 billion colony-forming units (CFU)/5 mL ampoule, administered 1 ampoule daily, during the first 90 days of life. The study examines effects on growth, digestive symptoms, immune markers, and microbial composition. Study Design: This randomized, blind, controlled clinical trial will enroll 180 healthy full-term cesarean-born infants at Hanoi Obstetrics and Gynecology Hospital. Intervention Description: Participants will be randomly assigned to three groups (n = 60 each). All groups will receive one 5-mL ampoule daily for 90 days: LiveSpo PREG-MOM, LiveSpo CONSY, or placebo. Stool samples will be collected at several follow-up time points to assess digestive health and microbial development. All products will be provided in blinded and coded packaging to maintain objectivity. Study Duration: 12 months

Conditions

Functional Gastrointestinal Disorders (FGIDs); Weight Loss

Keywords

Cesarean-born Infants; Gut Dysbiosis; Bacillus spore

Outcome Measures

Primary Outcomes (4)

• Change in stool frequency

  Change in daily stool frequency compared with baseline (day 0). Measurements at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.

  Days 0, 2, 9, 30, 60, and 90

• Change in stool consistency (Diapered Infant Stool Scale score)

  Change in stool consistency using the Diapered Infant Stool Scale (type 1-type 5) compared with baseline (day 0). Measurements at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.

  Days 0, 2, 9, 30, 60, and 90

• Change in regurgitation

  Change in regurgitation assessed by both frequency (number of regurgitation episodes per day) and severity (caregiver-reported severity), compared with baseline (day 0). Measurements will be obtained at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.

  Days 0, 2, 9, 30, 60, and 90

• Change in crying episodes

  Change in the number of crying episodes per day compared with baseline (day 0). Measurements at days 2, 9, 30, 60, and 90; days 2 and 9 serve as early supplementary timepoints.

  Days 0, 2, 9, 30, 60, and 90

Secondary Outcomes (5)

• Change in infant body weight

  Days 0, 2, 9, 30, 60, and 90

• Change in infant body length

  Days 0, 30, 60, and 90

• Change in infant head circumference

  Days 0, 30, 60, and 90

• Immune indicators in stool (cytokines and IgA)

  Days 0, 9, and 30

• Gut microbiota composition

  Days 0 and 30

Other Outcomes (3)

• Fecal calprotectin levels

  Days 0, 9, and 30

• Use of antibiotics during the study period

  Day 0 to Day 90

• Detection of probiotic Bacillus spores in stool

  Day 0 to Day 90

Study Arms (3)

Placebo group

PLACEBO COMPARATOR

The Placebo group receives reverse osmosis (RO) water with a dosage of 1 ampoule per day for 90 days.

Other: RO water

Pregmom group

EXPERIMENTAL

The Pregmom group receives RO water plus B. subtilis, B. clausii, and B. coagulans at 3 billion CFU/5 mL (LiveSpo PREG-MOM) with a dosage of 1 ampoule per day for 90 days.

Combination Product: LiveSpo PREG-MOM

Consy group

EXPERIMENTAL

The Consy group receives RO water plus B. subtilis, B. clausii, and B. coagulans at 4 billion CFU/5 mL (LiveSpo CONSY) with a dosage of 1 ampoule per day for 90 days.

Combination Product: LiveSpo CONSY

Interventions

RO water OTHER

RO water (Aquafina, PepsiCo) produced under ISO 9001:2015 and ISO 22000:2018 standards. The RO water ampoules are produced using a similar process as the LIVESPO PREG-MOM/CONSY but contain 5 mL of high-quality RO water from Aquafina.

Placebo group

LiveSpo PREG-MOM COMBINATION_PRODUCT

LiveSpo PREG-MOM has a registration number 7695/2020/ĐKSP issued by the Food Safety Department of the Ministry of Health in Vietnam.

Pregmom group

LiveSpo CONSY COMBINATION_PRODUCT

LiveSpo CONSY has a registration number 4165/2020/ĐKSP issued by the Food Safety Department of the Ministry of Health in Vietnam.

Consy group

Eligibility Criteria

• Age: 0 Days - 1 Day
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy term neonates delivered by cesarean section.
• Infants were born at term, ranging from 38 to 40 weeks' gestation.
• Birth weight appropriate for gestational age (AGA), defined as between the 10th and 90th percentiles for gestational age (≥P10 and ≤P90).
• The infant's parent(s) or legal guardian(s) provide written informed consent and agree to comply with study procedures.

You may not qualify if:

• For the neonate:
• Multiple births (twins, triplets, etc.)
• Birth weight outside the appropriate-for-gestational-age range: small for gestational age (SGA, \< P10) or large for gestational age (LGA, \> P90).
• Major congenital abnormalities affecting the hematologic, hepatobiliary, cardiovascular, renal/urinary, or gastrointestinal systems; severe inborn errors of metabolism; or suspected primary immunodeficiency.
• Prior exposure to systemic or enteral antibiotics (oral, IV, or IM) before the baseline assessment.
• Known allergy or intolerance to any component of the investigational product.
• Concurrent participation in another interventional clinical trial.
• The investigators judge the neonate to be unsuitable for participation.
• Parent(s) or legal guardian(s) who do not comply with study requirements or refuse to sign the informed consent.
• For the mother:
• Mother diagnosed with a serious or unstable medical condition involving the hepatobiliary, renal/urinary, cardiovascular, respiratory, endocrine/metabolic, or psychiatric systems.
• Mother who intends to use, or is prescribed, any other probiotic/prebiotic product for herself or the infant during the study period.

Sponsors & Collaborators

• Anabio R&D: lead
• Hanoi Obstetrics and Gynecology Hospital: collaborator

Study Sites (1)

Hanoi Obstetrics and Gynecology Hospital

Hanoi, Vietnam

Location

Related Publications (7)

• Long G, Hu Y, Tao E, Chen B, Shu X, Zheng W, Jiang M. The Influence of Cesarean Section on the Composition and Development of Gut Microbiota During the First 3 Months of Life. Front Microbiol. 2021 Aug 18;12:691312. doi: 10.3389/fmicb.2021.691312. eCollection 2021.

  PMID: 34489887 BACKGROUND

• Kelly NM, Keane JV, Gallimore RB, Bick D, Tribe RM. Neonatal weight loss and gain patterns in caesarean section born infants: integrative systematic review. Matern Child Nutr. 2020 Apr;16(2):e12914. doi: 10.1111/mcn.12914. Epub 2019 Nov 27.

  PMID: 31777183 BACKGROUND

• Ianiro G, Rizzatti G, Plomer M, Lopetuso L, Scaldaferri F, Franceschi F, Cammarota G, Gasbarrini A. Bacillus clausii for the Treatment of Acute Diarrhea in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2018 Aug 12;10(8):1074. doi: 10.3390/nu10081074.

  PMID: 30103531 BACKGROUND

• Gong Y, Zhong H, Wang J, Wang X, Huang L, Zou Y, Qin H, Yang R. Effect of Probiotic Supplementation on the Gut Microbiota Composition of Infants Delivered by Cesarean Section: An Exploratory, Randomized, Open-label, Parallel-controlled Trial. Curr Microbiol. 2023 Sep 15;80(11):341. doi: 10.1007/s00284-023-03444-4.

  PMID: 37712964 BACKGROUND

• Delfino E, Peano L, Wetzl RG, Gianni ML, Netto R, Consales A, Bettinelli ME, Morniroli D, Vielmi F, Mosca F, Montagnani L. Newborn Weight Loss as a Predictor of Persistence of Exclusive Breastfeeding up to 6 Months. Front Pediatr. 2022 Apr 7;10:871595. doi: 10.3389/fped.2022.871595. eCollection 2022.

  PMID: 35463877 BACKGROUND

• Colom J, Freitas D, Simon A, Brodkorb A, Buckley M, Deaton J, Winger AM. Presence and Germination of the Probiotic Bacillus subtilis DE111(R) in the Human Small Intestinal Tract: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study. Front Microbiol. 2021 Aug 2;12:715863. doi: 10.3389/fmicb.2021.715863. eCollection 2021.

  PMID: 34408741 BACKGROUND

• Bernardeau M, Lehtinen MJ, Forssten SD, Nurminen P. Importance of the gastrointestinal life cycle of Bacillus for probiotic functionality. J Food Sci Technol. 2017 Jul;54(8):2570-2584. doi: 10.1007/s13197-017-2688-3. Epub 2017 May 23.

  PMID: 28740315 BACKGROUND

MeSH Terms

Conditions

Gastrointestinal Diseases; Weight Loss

Condition Hierarchy (Ancestors)

Digestive System Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Hung T Mai, PhD

  Hanoi Obstetrics and Gynecology Hospital

  PRINCIPAL INVESTIGATOR

• Chuong C Nguyen

  Hanoi Obstetrics and Gynecology Hospital

  STUDY CHAIR

• Anh TV Nguyen, Assoc.Prof.PhD

  Anabio R&D

  STUDY CHAIR

Central Study Contacts

Hung T Mai, PhD

CONTACT

(+84) 988.855.888; bacsymaitronghung@gmail.com

Chuong C Nguyen

CONTACT

(+84)913368526; chuongnc2912@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2025
• First Posted: January 6, 2026
• Study Start: January 7, 2026
• Primary Completion (Estimated): September 7, 2026
• Study Completion (Estimated): January 7, 2027
• Last Updated: January 7, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data requests can be submitted 9 months after article publication and will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research. It will be provided following the review and approval of a study protocol, informed consent form (ICF), clinical study report (CSR), and Statistical Analysis Plan (SAP). For more information or to submit a request, please get in touch with anabio.rd2021@gmail.com

Locations

VN (1)